Project Summary/Abstract This revised R34 is responsive to RFA-MH-18-706, to the ongoing NIMH interest in Digital Health, and to the prior review. Most obesity and related complications in serious mental illness (SMI) occur in the context of chronic psychiatric illness. Behavioral interventions to reverse obesity in chronic SMI face challenges with long- term effectiveness, implementation and sustainability. Pharmacotherapies are limited to off-label treatments with modest effectiveness and/or serious adverse event risks. This application focuses on prevention of chronic obesity by adapting and pilot testing a prevention-focused, interactive obesity treatment approach (iOTA) for use in persons with early-phase SMI (eSMI) experiencing initial weight gain, overweight or early class I obesity. The intervention will be adapted from the most studied, effective iOTA (e.g., weight loss at 24 months), derived from the Diabetes Prevention Program. Planned adaptations address eSMI, prevention (focus on weight gain attenuation), and RDoC-relevant target mechanism engagement. The immediate parent iOTA for this application uses health coaches who extend their sustainable reach with scalable, inexpensive, semi-automated SMS messaging, a highly-utilized technology among low-income populations, to increase intervention engagement, effectiveness and cost-effectiveness. Using a formal evaluation process and specific implementation science framework, planned adaptations for this application address eSMI, prevention, and RDoC-relevant target mechanism engagement, hypothesizing increased health-related awareness, insight and self-efficacy for food intake and activity. Our overarching aim is to adapt and pilot a scalable, sustainable, prevention-focused iOTA for use in the broad community mental health center (CMHC) population of at-risk persons with eSMI, planning for future effectiveness testing in a fully-powered RCT and eventual large scale implementation. Specific Aim 1: Evaluate barriers and facilitators for intervention engagement, effectiveness and implementation, and identify needed adaptations of the prior iOTA for use in obesity attenuation in eSMI. Specific Aim 2: Adapt the prior iOTA for use in obesity attenuation in eSMI, aiming to maximize acceptability, engagement, sustainable reach and target engagement for eSMI. Specific Aim 3: Conduct a randomized pilot and feasibility study of iOTA-eSMI in a diverse sample of adults aged 18-45 with eSMI and initial weight gain, overweight or early class I obesity, comparing iOTA-eSMI to a health education control condition. The goal of this study is to measure feasibility, acceptability, tolerability, and target engagement, exploring effects on change in body weight from baseline with iOTA-eSMI compared to control. Secondary analyses will assess iOTA effects on RDoC domains relevant to needed psychophysical skills and self-efficacy, exploring the relationship between weight change and target engagement. 1